The goal of this project is to develop improved methods for the diagnosis and treatment of ocular inflammatory diseases in human patients of all ages including uveitis, scleritis, inflammatory diseases of the ocular surface such as the dry eye syndrome, and intraocular malignancies. Over the past year clinical studies have focused on examining the effectiveness of new therapeutic agents which act by blocking specific molecules known to play a role in the development of inflammation in the eye. One such medication is etanercept (Enbrel). Etanercept is a synthesized protein given by subcutaneous injection that binds to tumor necrosis factor (TNF) one of the important molecules that may cause arthritis in children and adults. We are currently recruiting for a study to determine the safety and efficacy of etanercept for the treatment of uveitis in children with juvenile rheumatoid arthritis (JRA) that are prone to develop chronic inflammation in the eye. Another new agent, the Humanized Anti-Tac monoclonal antibody (Zenepax, Daclizumab), also called HAT for short, is the product of translational bench-to-beside research performed in the NEI Laboratory of Immunology. Given by intravenous injection, HAT binds to activated T-cells that cause inflammation and damage in the eye in several diseases that are thought to be autoimmune in origin. Thus far, the majority of patients treated with HAT have been able to decrease the number and dose of other immunosuppressive medications such as prednisone, cyclosporine and methotrexate required to control their uveitis and have experienced stable or improved vision. Because of the success with HAT we have started a second protocol for patients with Behcet's disease and have plans for a future study to treat children with uveitis using HAT. Another example of translational bench-to-beside research resulted from the observation that pregnancy and the female hormones estrogen and progesterone can influence the severity of disease in an animal model of uveitis. The findings correlate with anecdotal observations that uveitis in women may improve during pregnancy and vary with the menstrual cycle. Based on this information a clinical protocol to determine the effect of pregnancy on patients with uveitis was developed. Dry eye is a condition that affects millions of Americans. Important studies performed in the NEI investigating the effect of treatment with topical cyclosporine for dry eye have revealed that inflammation on the ocular surface plays a key role in the development of this disease. As a result a new medication to treat dry eye is expected soon. Continuing studies on the pathogenesis of primary intraocular lymphoma have recently revealed the presence of DNA from human herpes virus type 8 (HHV-8) and the Epstein-Barr virus (EBV) in the lymphoma cells removed from the eye. These findings suggest that a viral agent may play a role in the development of this ocular malignancy. Another viral agent known to be associated with malignancy and ocular inflammation is the human T-cell lymphotrophic virus type I (HTLV-1). Examination of HTLV-1 infected patients in the NEI has revealed the presence new corneal findings. A protocol to further investigate the natural history of eye disease caused by HTLV-1 is in progress.